This study began as an efficacy study of interferon alfa-2a in patients with hairy cell leukemia. It was observed that most patients responded to interferon, but that very few complete responses were being obtained. Studies being done elsewhere confirmed the low complete remission rate. Once interferon was stopped, nearly uniformly disease progression requiring reinstitution of therapy was observed. There appear to be very few if any patients who will not require further therapy after 12 or 18 months of continuous interferon treatment. Because of these findings, we opted to administer interferon continuously to patients who were initially responsive to this drug. Of the 53 evaluable patients (of the 56 entered on this study), there was one complete remission, 34 partial remissions, 3 minor responses, 9 patients with stable disease and only 1 patient with disease progression. Thirty-two patients continue to receive interferon without interruption with a median duration of continuous interferon treatment of 60 months. Twenty-one patients discontinued interferon for a variety of reasons the most common of which being the development of acquired interferon resistance in association with interferon antibodies. Although it is clear from this study that the disease can be controlled in the long-term with interferon, longer follow-up will be necessary to determine if this form of therapy is better than intermittent therapy with interferon.